Fungal vaginitis, one of the vaginal diseases with high morbidity rate, is difficult to cure radically. In U.S. more than 75% women suffer from fungal vaginitis at least once in their life. About 5% of adult women suffer from repeated vaginal fungal infection, which is difficult to cure (Jack D. Sobel, MD.Candidal Vulvovaginitis, Clinical Obstetrics and Gynecology, 1993 Vol.36 (1): 153-165). The main clinical symptoms of these vaginal diseases include vulval pruritus, vaginal pain, leukorrhagia, dyspareunia, and urodynia. Therefore, this disease is harmful to women's health status as well as to their life quality.
There are various anti-fungal drugs for treating fungal vaginitis by directly inhibiting or killing fungi. The commonly used drugs include Ketoconazole, Fluconazole, Mikostatin and Clotrimazolum. They can be administered locally in the vagina or taken orally. But most of the local vaginal anti-fungal agents contain starch and/or lactose as auxiliaries, for example, as excipient. The inventor of this application has discovered that starch, lactose or other saccharides can significantly promote acid production by vaginal bacteria, increase vaginal acidity, thus promoting fungal growth in the vagina. Therefore the starch and/or lactose contained in the pharmaceutical composition are extremely unfavorable for treating vaginal fungal infection.
Furthermore, it is not easy to achieve the satisfactory curative effect by just using these anti-fungal drugs. For example, the curative rate of anti-fungal drugs is generally 75-80% for Mikostatin and 85-90% for glyoxaline anti-fungal drugs such as Ketoconazole, Treconazole, and Fluconazole (Jack D. Sobel). Even in those patients being cured by anti-fungal drugs, the disease often relapses in following menstrual periods after stopping the treatment.
The object of the present invention is to provide a pharmaceutical composition for reducing vaginal acidity, treating abnormally high vaginal acidity, vaginitis, fungal vaginitis associated with high vaginal acidity. This invention also relates to methods for treating abnormally high vaginal acidity, vaginitis associated with high vaginal acidity, especially for treating fungal vaginitis associated with high vaginal acidity.
In order to find a new pharmaceutical composition for treating fungal vaginitis, the inventor had conducted an extensive study and eventually developed a pharmaceutical composition of this invention. By using light microscopy, the inventor examined vaginal secretions from patients who had been clinically diagnosed as fungal vulvovaginitis. However, in many cases it was very difficult to confirm the fungal infection because little fungi had been found in vaginal secretions samples. After further study, it was found out surprisingly that, the vaginal acidity in such patients was abnormally high (vaginal pH value<4.0), which could result in the damage of vaginal mucous membranes alone. Therefore, these cases were actually related to abnormal enhancement of acidity in the vagina and could be called “high acidity vaginitis”. The inventor also noticed that “high acidity vaginitis” had a close relationship with repeated fungal vulvo-vaginitis. This is one of the reasons why it is difficult to cure the repeated fungal vaginitis by just using anti-fungal drugs.
The U.S. patent (U.S. Pat. No. 4,804,674) teaches a method for enhancing sperm motility, wherein amino acids and /or salts of amino acids are used to enhance sperm motility. These amino acids are mainly comprising aspartic acid, glutamic acid, arginine, histidine, asparagine, glutamine, and arginine aspartate. U.S. Pat. No. 4,804,674 does not indicate that the amino acids can reduce the acid production in the vagina. U.S. Pat. No. 4,804,674 does not mention the relationship between abnormal enhancement of vaginal acidity and fungal vaginitis, or that amino acids can be used to reverse the abnormally enhanced vaginal acidity, or to treat high acidity vaginitis and fungal vaginitis.
The U.S. patent U.S. Pat. No. 4,937,234 discloses a pharmaceutical composition of neutral salts of gluconic acid, wherein zinc gluconate is an effective bactericiocidal component. These amino acids include alanine, valine, isoleucine, proline, glycine, serine, threonine, asparagine, glutamine, lysine, arginine, histidine and mixtures thereof. They are also used as auxiliaries in the pharmaceutical composition of U.S. Pat. No. 4,937,234, wherein the main component is lysine. As shown in the examples 1 to 12 of U.S. Pat. No. 4,937,234, it is emphasized that amino acids can regulate and change the acidity of the composition to neutral, and thus reduces the stimulation of the composition and enhances the sterilization of zine agents. U.S. Pat. No. 4,937,234 particularly emphasizes that its pharmaceutical composition can be used on the neonates, old people, eyes and noses that are sensitive to acid, for treatment of diaper rash, skin dryness and vaginitis. Although different treatments and drugs are adopted for treating different types of vaginitis, U.S. Pat. No. 4,937,234 does not indicate the type of vaginitis. Furthermore, no information or data indicates or suggests whether the lysine also exerts treatment effect on vaginitis when used separately.